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Scholarly Interest Report
         
Charles R. Stewart
Professor
Professor of Biochemistry and Cell Biology
 
e-mail:crs@rice.edu
 
  • B.S. Zoology (1962) University of Wisconsin, Madison
  • Ph.D. Genetics (1967) Stanford University
 
Primary Department
   Department of BioSciences
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Department Affiliations
 
  • Institute of Biosciences and Bioengineering
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    Research Areas
     Molecular Genetics. Microbial Biotechnology. Bacteriophage biology.
     

    2013 Research Statement

     

    Infection of Bacillus subtilis by bacteriophage SPO1 causes profound changes in the genetic processes of the host cell. Stewart's Research Synthesis of host DNA, RNA, and protein is shut off, presumably to prevent those syntheses from competing with the corresponding phage biosyntheses for materials, energy, and access to biosynthetic machinery. Such global redirection of the cell's resources requires regulatory mechanisms of great sophistication and specificity, to eliminate the host-specific biosyntheses, while exactly the same processes, specific to the phage genome, proceed with enormous efficiency in the same cell. We are analyzing the mechanisms by which SPO1 accomplishes this takeover of the host cell. We have identified a cluster of 24 genes in the terminal redundancy of SPO1, which specifies most or all of the necessary machinery. By observing the effect of expression of each gene in uninfected cells, and the effect of mutational inactivation of each gene on the progress of infection, we are defining the specific roles of the 24 gene products. Activities that have been identified for specific gene products include: (1) shutoff of host DNA and RNA synthesis; (2) regulation of the timing of those shutoffs; (3) inhibition of host cell division; and (4) regulation of expression of the 24 genes. The broad spectrum bactericidal activity of some of these gene products makes them a potential basis for development of new antibiotics.

     

    Research Statement 2015

     

    Infection of Bacillus subtilis by bacteriophage SPO1 causes profound changes in the genetic processes of the host cell. Stewart's ResearchSynthesis of host DNA, RNA, and protein is shut off, presumably to prevent those syntheses from competing with the corresponding phage biosyntheses for materials, energy, and access to biosynthetic machinery. Such global redirection of the cell's resources requires regulatory mechanisms of great sophistication and specificity, to eliminate the host-specific biosyntheses, while exactly the same processes, specific to the phage genome, proceed with enormous efficiency in the same cell. We are analyzing the mechanisms by which SPO1 accomplishes this takeover of the host cell. We have identified a cluster of 24 genes in the terminal redundancy of SPO1, which specifies most or all of the necessary machinery. By observing the effect of expression of each gene in uninfected cells, and the effect of mutational inactivation of each gene on the progress of infection, we are defining the specific roles of the 24 gene products. Activities that have been identified for specific gene products include: (1) shutoff of host DNA and RNA synthesis; (2) regulation of the timing of those shutoffs; (3) inhibition of host cell division; and (4) regulation of expression of the 24 genes. The broad spectrum bactericidal activity of some of these gene products makes them a potential basis for development of 

     
    Teaching Areas
     Genetics, Molecular Biology, Microbiology, Virology
     
    Selected Publications
     Abstracts
     

    Haeusser, D.P., Karabunarlieva, E., Myles, B., Petti, A., Levin, P.A., Stewart, C.R., and Margolin, W. "Inhibition of B. subtilis cell division by gp56 of the SPO1 bacteriophage." Abstracts of the 4th ASM Conference on Prokaryotic Cell Biology and Development. , Abstract #126B (May 6-10, 2012)

     
     

    Stewart, C.R. et al. "Host-takeover in SPO1 Infection: Gene Functions; Timing of Host-Shutoff; Evolutionary Considerations; and the Terminal Redundancy.."  (August, 2009) : 1.

     
     

    Stewart, C.R. et al. "The genome of Bacillus subtilis bacteriophage SPO1 ."  (August, 2007) : G-3.

     
     

    Kvachadze, L., Stewart, C., et al. "Characterization of Staphylococcus basteriophage Sb-1 and phage-specific recombinant clones with lethal activity." Abstracts of 16th Evergreen International Phage Biology Meeting (2005) : G-26.

     
     

    Stewart, C.R., and Yip, T. "Activities specified by the "host-takeover module" of B. subtilis phage SPO1." Abstracts of 16th Evergreen International Phage Biology Meeting (2005) : M-79.

     
     

    Yip, T.K.S., Laughlin, L.J., Myles, B., and Stewart, C.R. "Role of genes 37-40 in host takeover during SPO1 infectin of B. subtilis." Abstracts of 16th Evergreen International Phage Biology Meeting (2005) : S-88.

     
     

    Laughlin, L.J., and Stewart, C.R. "Role of genes 37 to 40 in host-takeover during SPO1 infection of Bacillus subtilis." Abstracts of the 104th General Meeting of the American Society for Microbiology, New Orleans (2004) : 392.

     
     

    Yip, T.K., Laughlin, L.J., and Stewart, C.R. "Role of genes 37 to 40 in host-takeover during SPO1 infection of B. subtilis." Abstracts of the American Society for Microbiology Conference on the New Phage Biology, Key Biscayne, Florida (2004) : 64.

     
     

    Sampath, A., and Stewart, C. "Regulation of gene expression and host-takeover during infection of B. subtilis by bacteriophage SPO1." Abstracts of 15th Evergreen International Phage Conference (2003)

     
     

    Sampath, A., Myles, B., Cox, K., Chen, L., and Stewart, C. "Role of specific genes in host-takeover of B. subtilis by bacteriophage SPO1." Abstracts of 102nd General Meeting, May 19-23, 2002 (2002) : 302.

     
     

    Sampath, A., Monroe-Augustus, M, Cox, K., and Stewart, C. "Role of SPO1 genes 44, 50, and 51 in host-takeover and bacterial cell death." In Abstracts of the Fourteenth Evergreen International Phage Biology Meeting, Aug. 8-13 (2001)

     
     

    Sampath, A., Myles, B., Cox, K., Chen, L.A., Petti, A. and Stewart, C. "Genetic analysis of host-takeover in SPO1 infection of B. subtilis." In Abstracts of the Fourteenth Evergreen International Phage Biology Meeting, Poster Section, Aug. 8-13 (2001)

     
     

    Stewart, C. Myles, B., Cox, K. , Chen, L.A., Petti, A. and Sampath, A. "Effects of SPO1 host-takeover genes on bacterial physiology and viability." In Abstracts of the Fourteenth Evergreen International Phage Biology Meeting, Aug. 8-13 (2001)

     
     Refereed articles
     

    Tevdoradze, E., Kvachadze, L., Kutateladze, M., and Stewart, C.R. "Bactericidal genes of Staphylococcal bacteriophage Sb-1." Current Microbiology, 68 (2014) : 204-210.

     
     

    Stewart, C.R., Deery, W.J., Egan, E.S.K., Myles, B., and Petti, A. A. "The product of SPO1 gene 56 inhibits host cell division during infection of Bacillus subtilis by bacteriophage SPO1." Virology, 447 (2013) : 249-253.

     
     

    Stewart, C.R., Casjens, S.R., Cresawn, S.G., Houtz, J.M., Smith, A.L., Ford, M.E., Peebles, C.L., Hatfull, G.F., Hendrix, R.W., Huang, W.M., Pedulla, M.I. "The genome of Bacillus subtilis bacteriophage SPO1." J. Mol. Biol., 388 (2009) : 48-70.

     
     

    Stewart, C.R., Yip, T.K., Myles, B., Laughlin, L. "Roles of genes 38, 39, and 40 in shutoff of host biosyntheses during infection of Bacillus subtilis by bacteriophage SPO1." Virology, 392 (2009) : 271-274.

     
     

    Sampath, A., and Stewart, C. "Roles of genes 44, 50, and 51 in regulating gene expression and host-takeover during infection of Bacillus subtilis by bacteriophage SPO1." J. Bacteriology, 186 (2004) : 1785-1792.

     
     

    Stewart, C.R., Gaslightwala, I., Hinata, K., Krolikowski, K.A., Needleman, D.S., Peng, A.S.-Y., Peterman, M.A., Tobias, A., and Wei, P. "Genes and Regulatory Sites of the 'Host Takeover Module' in the Terminal Redundancy of Bacillus subtilis Bacteriophage SPO1." Virology, 246 (1998) : 329-340.

     
     

    Stewart, C.R. "Bacteriocidal Genes and Gene Products of Bacillus subtilis Bacteriophage SPO1." Invention Disclosure (1997)

     
     

    Curran, J.F., and Stewart, C.R. "Cloning and Mapping of the SPO1 Genome." Virology, 142 (1985) : 78-97.

     
     

    Wei, P., and Stewart, C.R. "Genes that Protect Against the Host-Killing Activity of the E3 Protein of Bacillus subtilis Bacteriophage SPO1." J. Bacteriol., 177 (1995) : 2933-2937.

     
     

    Wei, P., and Stewart, C.R. "A Cytotoxic Early Gene of Bacillus subtilis Bacteriophage SPO1." J. Bacteriol., 175 (1993) : 7887-7900.

     
     

    Curran, J.F., and Stewart, C.R. "Transcription of B. subtilis Plasmid pBD64, and Expression of Bacteriophage SPO1 Genes Cloned Therein." Virology, 142 (1985) : 98-111.

     
     

    Stewart, C.R. "Dissection of HA20, a Double Mutant of Bacteriophage SPO1." J. Virol., 49 (1984) : 300-301.

     
     

    Curran, J.F., and Stewart, C.R. "Recombination and Expression of a Cloned Fragment of the DNA of Bacillus subtilis Bacteriophage SPO1." Virology, 120 (1982) : 307-317.

     
     

    Stewart, C.R., and Franck, M. " Limited role of parental DNA in replication during infection by Bacillus subtilis phage SP01." Virology, 110 (1981) : 221-224.

     
     

    Stewart, C.R., and Franck, M. "Predominance of bacteriophage SP82 over bacteriophage SP01 in mixed infections of Bacillus subtilis." J. Virol., 38 (1981) : 1081-1083.

     
     

    Cregg, J.M., and Stewart, C.R. "EcoRI cleavage of DNA from phage SP01." Virology, 85 (1978) : 601-605.

     
     

    Cregg, J.M., and Stewart, C.R. "Terminal Redundancy of "High Frequency of Recombination" Markers of Bacillus subtilis Phage SP01." Virology, 86 (1978) : 530-541.

     
     

    Cregg, J.M., and Stewart, C.R. "Timing of Initiation of DNA Replication in SP01 Infection of Bacillus subtilis." Virology, 80 (1977) : 289-296.

     
     

    Glassberg, J.S., Franck, M., and Stewart, C.R. "Initiation and Termination Mutants of Bacillus subtilis phage SP01." J. Virol., 21 (1977) : 147-152.

     
     

    Glassberg, J.S., Franck, M., and Stewart, C.R. "Multiple Origins of Replication for Bacteriophage SP01." Virology, 78 (1977) : 433-441.

     
     

    Stewart, C.R., Click, B., and Tole, M.F. "DNA Replication and Late Protein Synthesis during SP82 Infection of Bacillus subtilis." Virology, 50 (1972) : 653-663.

     
     

    Stewart, C.R., Cater, M., and Click, B. "Lysis of Bacillus subtilis by bacteriophage SP82 in the absence of DNA synthesis." Virology, 46 (1971) : 327-336.

     
     Book chapters
     

    Stewart, C. "Analysis of Host-takeover during SPO1 infection of Bcillus subtilis" in "Bacteriophages: Methods and Protocols", eds Clokie, M., Lavigne, R. and Kropinski, A. (in press, 2015).

     
     

    Stewart, C. "Site-specific Mutagenesis of Bcillus subtilis phage SPO1" in "Bacteriophages: Methods and Protocols", eds Clokie, M., Lavigne, R. and Kropinski, A. (in press, 2015).

     
     

    Stewart, C. "Analysis of Host-takeover during SPO1 infection of Bacillus subtilis" in "Bacteriophages: Methods and Protocols", eds Clokie, M., Lavigne, R. and Kropinski, A. (submitted for publication, 2014).

     
     

    Stewart, C. "Site-specific Mutagenesis of Bacillus subtilis phage SPO1" in "Bacteriophages: Methods and Protocols", eds Clokie, M., Lavigne, R. and Kropinski, A. (submitted for publication, 2014).

     

     
     

    Stewart, C.R. et al. "SPO1-like Viruses." The Springer Index of Viruses, 2nd edition (2011 ) : 931-939.

     
     

    Stewart, C.R. "Bacteriophage SPO1." in Encyclopedia of Virology, 2nd Edition (Webster, R.G., and Granoff, A., eds.) (1999) : 1681-1685.

     
     

    Stewart, C.R. "SPO1 and Related Bacteriophases." Bacillus subtilis and Other Gram-Positive Bacteria (1993) : 813-829.

     
     

    Stewart, C.R. "Bacteriophage SPO1." Bacteriophages, Vol. I (1988) : 477-515.

     
    Presentations
     Seminar Speaker
     

    "Host-takeover in SPO1 infection: Gene functions; timing of host shutoff; evoltionary consideration; and the terminal redundancy." Evergreen International Phage Biology Meeting, Olympia, WA. (August 9-14, 2009)

     
     

    "The Genome of Bacillus subtilis Bacteriophage SPO1." 17th Evergreen International Phage Biology Meeting, Olympia, Washington. (August 12-17, 2007)

     
     

    "The Genome of Bacillus subtilis Bacteriophage SPO1." 17th Evergreen International Phage Biology Meeting, Olympia, Washington. (August 12-17, 2007)

     
     

    "Effects of SPO1 Host-takeover Genes on Bacterial Physiology and Viability." Fourteenth Evergreen International Phage Biology Meeting, (Aug. 8-13, 2001)

     
     

    "Genetic Analysis of Host-takeover in SPO1 infection of B. subtilis." Fourteenth Evergreen International Phage Biology Meeting, Poster Section, (Aug. 8-13, 2001)

     
     

    "Role of SPO1 Genes 44, 50, and 51 in Host-takeover and Bacterial Cell Death." Fourteenth Evergreen International Phage Biology Meeting, (Aug. 8-13, 2001)

     
     

    "A Host-takeover Module in the Terminal Redundancy of B. subtilis Phage SPO1." 12th Evergreen International Phage Biology Meeting, Olympia, Washington. (July 16 - 20, 1998)

     
     

    "Host-Lethal Genes. SPO1 Gene 56 Product Inhibits B. subtilis Cell Division." 12th Evergreen International Phage Biology Meeting, Olympia, Washington. (July 16 - 20, 1998) With Allegra Petti

     
     

    "SPO1 Gene 56 Product Inhibits B. subtilis Cell Division." 98th General Meeting of the American Society for Microbiology, Atlanta, Georgia. (May 17 - 21, 1998) With Allegra Petti

     
     

    "The Early Genes of Bacillus subtilis Bacteriophage SPO1." 98th General Meeting of the American Society for Microbiology, Atlanta, Georgia. (May 17 - 21, 1998)

     
    Supervised Theses & Dissertations
     Luise Rogg, Ph.D. Cloning and characterization of IAA28, a gene involved in suppressing lateral root development and mediating auxin responses in Arabidopsis thaliana. (2002) (Thesis Committee Member)

     Wafa Elbjeirami, Ph.D. Genetic Modification of Smooth Muscle Cells to Enhance the Performance of Tissue Engineered Vascular Grafts. (2003) (Thesis Committee Member)

     Philip Caldwell, Ph.D. Ras Signaling in Either Prothoracic Gland Cells or Cholinergic Neurons of Drosophila melanogaster Regulates Fly Size. (2007) (Thesis Committee Member)

     Yitai Tang, Ph.D. Characterization of CnrN-mediated Size Regulation in Dictyostelium. (2007) (Thesis Committee Member)

     Michael Texada, Ph.D. Characterization of the gravitaxis-related protein Yuri Gagarin through genetic and biochemical approaches. (2008) (Thesis Committee Member)

     Leighann Sullivan, Ph.D. Molecular and Genomic Analyses in Clostridium acetobutylicum. (2008) (Thesis Committee Member)

     Eric Howlett, Ph.D. A PI3-Kinase Mediated Negative Feedback Regulates Neuronal Excitability at the Drosophila Neuromuscular Junction. (2009) (Thesis Committee Member)

     Tameson Yip, M.A. The Mystery of SPO1 Delayed Early Genes . (2009) (Thesis Director)

     Sonia Bjorum, Ph.D. A lov Story: A role for jim lovell in Drosophila neural development and fertility.. (2010) (Thesis Committee Member)

     Andres Benitez, Ph.D. The Biophysical Basis for Adaptation: Predicting Evolutionary Outcomes from Physicochemical Properties. (2012) (Thesis Committee Member)

     Aaron Collier, Ph.D. Initiation of RNA polymerization and polymerase encapsidation by a human infecting strain of Picobirnavirus. (2014) (Thesis Committee Member)

     Sam Kwiatkowski, Ph.D. Role of Pro- and Anti-angiogenic factors during formation of the periocular vasculature and establishment of corneal avascularity. (Thesis Committee Member)

     Yanlin Fan, PhD Structure and function studies of Orsay virus. (Thesis Committee Member)

    Awards, Prizes, & Fellowships
     Member, American Society for Microbiology

     Member, American Association for Advancement of Science